Anthony Mahowald

Last updated

Anthony Mahowald (born November 24, 1932) is a molecular genetics and cellular biologist who served as the department chair of the molecular genetics and cellular biology department at the University of Chicago. [1] His lab focused on the fruit fly Drosophila melanogaster , specifically focusing on controlling the genetic aspects of major developmental events. [1] His major research breakthroughs included the study of the stem cell niche, endocycles, and various types of actin.

Contents

Personal life

Anthony Mahowald is married and has three children. [2]

Educational career

Anthony Mahowald was born in Albany, Minnesota, on November 24, 1932. [3] Mahowald received a bachelor's degree from Spring Hill College in Mobile, Alabama. [3] Following his undergraduate studies, Mahowald earned his Ph.D. from Johns Hopkins University in 1962. [3] At Johns Hopkins, Mahowald studied the structure of pole cells and polar granules in Drosophila melanogaster. [4] Both his undergraduate and doctoral degrees were in the field of biology.

Professional career

Mahowald has worked in many universities in his academic career. From 1972 to 1982, he started his career at Marquette University, while also working for the Institute of Cancer Research in Philadelphia, Pennsylvania. [3] Then, he accepted a position at Indiana University from 1972 to 1982. [3] He then moved on to Case Western Reserve University from 1982 to 1990. [3] [5] Finally, from 1990 to 2002, Mahowald was employed at the University of Chicago as the department chair for molecular genetics and cellular biology. [3] In 2002, he retired from academia and currently works as an emeritus at the University of Chicago. [1]

Awards and associations

Mahowald is a member of a wide range of prestigious organizations. He is a part of the American Association for the Advancement of Science, Society of Scholars at Johns Hopkins University, American Academy of Arts and Sciences, the Woodrow Wilson Foundation, the Genetics Society of America, the American Society of Cell Biology, the Society of Developmental Biology, and the National Academy of Science. [3]

Research and scientific contributions

Drosophila melanogaster under microscope Drosophila melanogaster under microscope.jpg
Drosophila melanogaster under microscope

The majority of his research centered around the common fruit fly and other insects for developmental and genetic studies. [6] [ failed verification ]

One of Malhowald's groundbreaking articles involve the study of the stem cell niche, which is a specialized environment where adult stem cells reside in some insects and amphibians. [7] This area helps to keep stem cells in an undifferentiated state through short-range signaling. [8] Mahowald discovered that this area, and specifically the e-cadherin-based stem cell adhesion, is vital in maintaining the Drosophila germline stem cells. [8] These stem cells are important to the reproduction of Drosophila as they turn into sperm cells. In Drosophila testicles, the Leukocyte-antigen-related (LAR) receptor tyrosine phosphatase targets selection and synapse formation with nerve cells. [8] After testing, it was discovered that the receptor expression is increased in the analysis of testicles containing higher numbers of early germ cells and cyst cells. [8] After analysis of this data and further testing of his own, Mahowald discovered that the LAR expressed in the testicles retains germline stem cells at the niche through the increased E-cadherin-based adhesion. [8]

Some of Mahowald's most recent work centers around the study of endocycles. These are cell cycles that do not have a mitotic phase. In other words, cells continuously duplicate their genetic information without division into two cells. [9] This creates very large cells, but their genetic information cannot be organized and separated into chromosomes due to inhibition of cyclin-dependent kinase activity. Mahowald discovered pre-mitotic endocycles in rectal non-cancerous polyploid cells in Drosophila. [10] The endocycling creates a polyploid cell, and these polyploid have high error-rates, suggesting that there will be an accumulation of cells with incorrect number of chromosomes. [9] He argues that pre-mitotic endocycling is essential for non-cancerous polyploid development, specifically in papillary development. [10] While organisms would die from the accumulation of aneuploid, Mahowald found that, in this instance, significant changes in survival rates were not observed. [10] Thus, he and his team directly disproved previous thoughts that aneuploidy decreases survivability in various insects, especially flies. [11]

Mahowald also studied the actin and the various genes that code for very similar types of actin in an organism. Mahowald was concerned as to why organisms have multiple, very similar, genes that encode for the same proteins with only a few amino acids different. To attempt to answer this question, Mahowald and team isolated two actin genes, Act42A and Act5C, with only two amino acids being different between the two genes, and both are present in all cells in the Drosophila during development. [12]

Other researchers had established that multiple isoforms are crucial for development. It was determined that the small differences make actin filaments that do have different functions, such as cytoplasmic functions and muscular functions. [13] Indeed, Mahowald established that there is a need for multiple forms of actin due to the large quantity of actin needed in a cell, along with the fact that some cells have different microfilament-based needs. However, he set out to determine if these actin filaments could be interchanged due to their similarity in structure.

Mahowald focused on cytoplasmic actin genes instead of muscular actin due to the multifunctional nature of cytoplasmic actin when compared to muscular actin. [14] Using genomic DNA and Reverse Transcription PCR Sequences, Mahowald determined that these amino acid substitutions in Act5C and Act42A did not occur in regions of the actin molecule where actin binding proteins interact. [12] By using the Drosophila as an easily controlled genetic system, Mahowald and his team discovered that mutations in the Act5C gene caused organism death, indicating that Act5C did have an important and isolated function. [12] However, a hybrid gene containing Act42A prevented organism death, indicating that the amino acid differences between the two isoforms are not significant. [12] Despite all of this, Mahowald concluded that tissues rich in Act5C gene expression cannot adequately function with only the Act42A isoform. [12] In other words, while very similar in genetic sequencing, the various isoforms of actin are important to the survivability and functionality of the Drosophila.

Related Research Articles

<span class="mw-page-title-main">Meiosis</span> Cell division producing haploid gametes

Meiosis is a special type of cell division of germ cells and apicomplexans in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately result in four cells with only one copy of each chromosome (haploid). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and a female will fuse to create a cell with two copies of each chromosome again, the zygote.

<span class="mw-page-title-main">Mutation</span> Alteration in the nucleotide sequence of a genome

In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA, which then may undergo error-prone repair, cause an error during other forms of repair, or cause an error during replication. Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements.

<span class="mw-page-title-main">Mitosis</span> Process in which chromosomes are replicated and separated into two new identical nuclei

Mitosis is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis is an equational division which gives rise to genetically identical cells in which the total number of chromosomes is maintained. Mitosis is preceded by the S phase of interphase and is followed by telophase and cytokinesis; which divides the cytoplasm, organelles and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. The different stages of mitosis altogether define the mitotic phase of a cell cycle—the division of the mother cell into two daughter cells genetically identical to each other.

<span class="mw-page-title-main">Germline</span> Population of a multicellular organisms cells that pass on their genetic material to the progeny

In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. They are usually differentiated to perform this function and segregated in a specific place away from other bodily cells.

Gene duplication is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene. Gene duplications can arise as products of several types of errors in DNA replication and repair machinery as well as through fortuitous capture by selfish genetic elements. Common sources of gene duplications include ectopic recombination, retrotransposition event, aneuploidy, polyploidy, and replication slippage.

Escargot (esg) is a transcription factor expressed in Drosophila melanogaster. It is responsible for the maintenance of intestinal stem cells and is used as a marker for those types of cells in Drosophila. Apart from its expression in the gut, esg is also expressed in expressed in germline stem cells and cyst stem cells of the testis and, during development, in neural stem cells and imaginal disks.

<span class="mw-page-title-main">Mosaic (genetics)</span> Condition in multi-cellular organisms

Mosaicism or genetic mosaicism is a condition in which a multicellular organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized egg. Mosaicism is one of several possible causes of chimerism, wherein a single organism is composed of cells with more than one distinct genotype.

Intragenomic conflict refers to the evolutionary phenomenon where genes have phenotypic effects that promote their own transmission in detriment of the transmission of other genes that reside in the same genome. The selfish gene theory postulates that natural selection will increase the frequency of those genes whose phenotypic effects cause their transmission to new organisms, and most genes achieve this by cooperating with other genes in the same genome to build an organism capable of reproducing and/or helping kin to reproduce. The assumption of the prevalence of intragenomic cooperation underlies the organism-centered concept of inclusive fitness. However, conflict among genes in the same genome may arise both in events related to reproduction and altruism.

Endoreduplication is replication of the nuclear genome in the absence of mitosis, which leads to elevated nuclear gene content and polyploidy. Endoreplication can be understood simply as a variant form of the mitotic cell cycle (G1-S-G2-M) in which mitosis is circumvented entirely, due to modulation of cyclin-dependent kinase (CDK) activity. Examples of endoreplication characterized in arthropod, mammalian, and plant species suggest that it is a universal developmental mechanism responsible for the differentiation and morphogenesis of cell types that fulfill an array of biological functions. While endoreplication is often limited to specific cell types in animals, it is considerably more widespread in plants, such that polyploidy can be detected in the majority of plant tissues.

Mitotic recombination is a type of genetic recombination that may occur in somatic cells during their preparation for mitosis in both sexual and asexual organisms. In asexual organisms, the study of mitotic recombination is one way to understand genetic linkage because it is the only source of recombination within an individual. Additionally, mitotic recombination can result in the expression of recessive alleles in an otherwise heterozygous individual. This expression has important implications for the study of tumorigenesis and lethal recessive alleles. Mitotic homologous recombination occurs mainly between sister chromatids subsequent to replication. Inter-sister homologous recombination is ordinarily genetically silent. During mitosis the incidence of recombination between non-sister homologous chromatids is only about 1% of that between sister chromatids.

<span class="mw-page-title-main">Protein 4.1</span> Protein-coding gene in the species Homo sapiens

Protein 4.1,, is a protein associated with the cytoskeleton that in humans is encoded by the EPB41 gene. Protein 4.1 is a major structural element of the erythrocyte membrane skeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction. Protein 4.1 interacts with spectrin and short actin filaments to form the erythrocyte membrane skeleton. Mutations of spectrin and protein 4.1 are associated with elliptocytosis or spherocytosis and anemia of varying severity.

Stem-cell niche refers to a microenvironment, within the specific anatomic location where stem cells are found, which interacts with stem cells to regulate cell fate. The word 'niche' can be in reference to the in vivo or in vitro stem-cell microenvironment. During embryonic development, various niche factors act on embryonic stem cells to alter gene expression, and induce their proliferation or differentiation for the development of the fetus. Within the human body, stem-cell niches maintain adult stem cells in a quiescent state, but after tissue injury, the surrounding micro-environment actively signals to stem cells to promote either self-renewal or differentiation to form new tissues. Several factors are important to regulate stem-cell characteristics within the niche: cell–cell interactions between stem cells, as well as interactions between stem cells and neighbouring differentiated cells, interactions between stem cells and adhesion molecules, extracellular matrix components, the oxygen tension, growth factors, cytokines, and the physicochemical nature of the environment including the pH, ionic strength and metabolites, like ATP, are also important. The stem cells and niche may induce each other during development and reciprocally signal to maintain each other during adulthood.

<span class="mw-page-title-main">Animal testing on invertebrates</span> Overview article

Most animal testing involves invertebrates, especially Drosophila melanogaster, a fruit fly, and Caenorhabditis elegans, a nematode. These animals offer scientists many advantages over vertebrates, including their short life cycle, simple anatomy and the ease with which large numbers of individuals may be studied. Invertebrates are often cost-effective, as thousands of flies or nematodes can be housed in a single room.

<span class="mw-page-title-main">DCTN1</span> Protein-coding gene in the species Homo sapiens

Dynactin subunit 1 is a protein that in humans is encoded by the DCTN1 gene.

Allan C. Spradling is an American scientist and principal investigator at the Carnegie Institution for Science and the Howard Hughes Medical Institute who studies egg development in the model organism, Drosophila melanogaster, a fruit fly. He is considered a leading researcher in the developmental genetics of the fruit fly egg and has developed a number of techniques in his career that have led to greater understanding of fruit fly genetics including contributions to sequencing its genome. He is also an adjunct professor at Johns Hopkins University and at the Johns Hopkins University School of Medicine.

Norbert Perrimon is a French geneticist and developmental biologist. He is the James Stillman Professor of Developmental Biology in the Department of Genetics at Harvard Medical School, an Investigator at the Howard Hughes Medical Institute, and an Associate of the Broad Institute. He is known for developing a number of techniques for used in genetic research with Drosophila melanogaster, as well as specific substantive contributions to signal transduction, developmental biology and physiology.

Oogonial stem cells (OSCs), also known as egg precursor cells or female germline cells, are diploid germline cells with stem cell characteristics: the ability to renew and differentiate into other cell types, different from their tissue of origin. Present in invertebrates and some lower vertebrate species, they have been extensively studied in Caenorhabditis elegans, Drosophila melanogaster. OSCs allow the production of new female reproductive cells (oocytes) by the process of oogenesis during an organism's reproductive life.

Renata Homem de Gouveia Xavier de Basto is a researcher in cell and developmental biology. She is currently a team leader at the Institut Curie in Paris. She is also the deputy director of the CNRS research Unit UMR144 'Cell biology and cancer' at the Institut Curie which, comprises 14 research teams.

A somatic mutation is a change in the DNA sequence of a somatic cell of a multicellular organism with dedicated reproductive cells; that is, any mutation that occurs in a cell other than a gamete, germ cell, or gametocyte. Unlike germline mutations, which can be passed on to the descendants of an organism, somatic mutations are not usually transmitted to descendants. This distinction is blurred in plants, which lack a dedicated germline, and in those animals that can reproduce asexually through mechanisms such as budding, as in members of the cnidarian genus Hydra.

The germ cell nest forms in the ovaries during their development. The nest consists of multiple interconnected oogonia formed by incomplete cell division. The interconnected oogonia are surrounded by somatic cells called granulosa cells. Later on in development, the germ cell nests break down through invasion of granulosa cells. The result is individual oogonia surrounded by a single layer of granulosa cells. There is also a comparative germ cell nest structure in the developing spermatogonia, with interconnected intracellular cytoplasmic bridges.

References

  1. 1 2 3 "Anthony P. Mahowald, PhD | Department of Molecular Genetics and Cell Biology". The University of Chicago. Retrieved April 10, 2021.
  2. ↑ "Head of University of Chicago Biology Department, Anthony P. Mahowald, PhD Helps Upgrade Leo High School Science Programs 2007". leoalumni.org. Retrieved April 10, 2021.
  3. 1 2 3 4 5 6 7 8 "Anthony Mahowald: University Honors and Awards". Indiana University. Retrieved April 10, 2021.
  4. ↑ Mahowald AP (December 1962). "Fine structure of pole cells and polar granules inDrosophila melanogaster". Journal of Experimental Zoology. 151 (3): 201–215. Bibcode:1962JEZ...151..201M. doi:10.1002/jez.1401510302. ISSN   0022-104X.
  5. ↑ Perrimon N, Engstrom L, Mahowald AP (September 1985). "Developmental genetics of the 2C-D region of the Drosophila X chromosome". Genetics. 111 (1): 23–41. doi:10.1093/genetics/111.1.23. PMC   1202596 . PMID   3928431.
  6. ↑ "An introduction to fruit flies". The Berg Lab. April 23, 2015. Retrieved April 10, 2021.
  7. ↑ Ferraro F, Celso CL, Scadden D (2010). "Adult Stem Cels and Their Niches". The Cell Biology of Stem Cells. Advances in Experimental Medicine and Biology. Vol. 695. pp. 155–68. doi:10.1007/978-1-4419-7037-4_11. ISBN   978-1-4419-7036-7. PMC   4020242 . PMID   21222205.
  8. 1 2 3 4 5 Srinivasan S, Mahowald AP, Fuller MT (April 2012). "The receptor tyrosine phosphatase Lar regulates adhesion between Drosophila male germline stem cells and the niche". Development. 139 (8): 1381–90. doi:10.1242/dev.070052. PMC   3308176 . PMID   22378638.
  9. 1 2 Edgar BA, Zielke N, Gutierrez C (March 2014). "Endocycles: a recurrent evolutionary innovation for post-mitotic cell growth". Nature Reviews. Molecular Cell Biology. 15 (3): 197–210. doi:10.1038/nrm3756. PMID   24556841. S2CID   641731.
  10. 1 2 3 Schoenfelder KP, Montague RA, Paramore SV, Lennox AL, Mahowald AP, Fox DT (September 2014). "Indispensable pre-mitotic endocycles promote aneuploidy in the Drosophila rectum". Development. 141 (18): 3551–60. doi:10.1242/dev.109850. PMC   6517832 . PMID   25142462.
  11. ↑ Lindsley DL, Sandler L, Baker BS, Carpenter AT, Denell RE, Hall JC, et al. (May 1972). "Segmental aneuploidy and the genetic gross structure of the Drosophila genome". Genetics. 71 (1): 157–84. doi:10.1093/genetics/71.1.157. PMC   1212769 . PMID   4624779.
  12. 1 2 3 4 5 Fyrberg EA, Mahaffey JW, Bond BJ, Davidson N (May 1983). "Transcripts of the six Drosophila actin genes accumulate in a stage- and tissue-specific manner". Cell. 33 (1): 115–23. doi:10.1016/0092-8674(83)90340-9. PMID   6432334. S2CID   23746956.
  13. ↑ Herman IM (February 1993). "Actin isoforms". Current Opinion in Cell Biology. 5 (1): 48–55. doi:10.1016/S0955-0674(05)80007-9. PMID   8448030.
  14. ↑ Storti RV, Rich A (July 1976). "Chick cytoplasmic actin and muscle actin have different structural genes". Proceedings of the National Academy of Sciences of the United States of America. 73 (7): 2346–50. Bibcode:1976PNAS...73.2346S. doi: 10.1073/pnas.73.7.2346 . PMC   430559 . PMID   1065885.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.